Low volume resuscitation in septic shock

1. Low volume resuscitation in septic shock Sunghoon Park Department of Pulmonary, Allergy and Critical Care Medicine Hallym University Sacred Heart Hospital

2. Self et al Ann Emerg Med. 2018;72:457-466

3. With EGDT in severe sepsis Fluid overload was found in 67% at day 1 in 48% at day 3 Fluid overload was ass/with ↑Diuretics ↑Thoracentesis ↑Hospital mortality

4. Higher fluid balance increased the risk of death from sepsis in observational data 84 countries and 730 ICUs Sakr et al. Crit Care Med 2017;45:386-394

5. Fluid resuscitation > 5L can be detrimental! 2013 Premier hospital discharge database in the USA N=23,513 4.4 L Marik et al Intensive Care Med 2017;43:625-632

6. Timeto completion of IV fluid bolus infusion was not associated with mortality. N=49,333at 149 hospitals Seymour et al New Engl J Med 2017;376:2235-2244

7. RCTs with negative impact of fluids African children, 24-mo old, Malaria (+) of 57% FEAST trial Maitland et al. NEJM. 2011;364:2483-2495 Open-label RCT, Zambian adults with HIV pts of 89.5%, Simplified Severe Sepsis Protocol 2 trial Andrews et al. JAMA. 2017;318:1233-1240. 36 yrs, suspected TB of 62%, Alb 2.2, only one MV pt

8. Caveats with fluid administrations • The purpose of fluids is to increase preload, but it does not always lead to increase in C.O. • Fluid boluses can augment hemodynamic parameters but its’ effect can be transient. • Even after hemodynamic improvement (MAP, C.O., CVP), impaired microcirculation or lactate(↑) can still persist. • Fluid overload can aggravate microcirculation.

9. Improved microcirculation only in sepsis survivors after day 1 Video images in buccal mucosa (18 pediatrics) FCD = functional capillary density Top et al. Crit Care Med 2011;39:8-13

10. Sublingual microcirculation was not improved by fluid administration in late phase N= 60 48 h 24 h 1L for 30 min Ospina-Tascon et al. Intensive care med 2010;36:949-955

11. Microcirculation becomes dissociated from macrocirculation Hermandez G and Teboul JL. Intensive care med 2016;42:1621-4

12. When to stop resuscitation? Flow dependent Non-flow dependent Another mechanisms Risk of over-resuscitation Normalization of macro-circulatory variables, but still abnormal micro-circulatory variables Hernandez et al. Annals of Intensive Care 2014;4:30

13. Is there a role for targeting microcirculation during early resuscitation? • ScvO2 • Lactate • P(v-a)CO2

14. Definitionandmechanism of ScvO2isnot easy to understand. HF, MODS, Anemia DO2/VO2 = 2:1 DO2/VO2 = 5:1 ScvO2 80% 75% 50% O2 ER Lactate

15. Lactate clearance is noninferior to ScvO2 N =300 “But, achievement of only ScvO2 goal was associated with higher mortality compared with achievement of only the lactate clearance (41% vs 8%)” Jones et al. JAMA 2010;303:739-46

16. Lactate clearance > 20% per 2 h Open RCT, N =348 Hospital mortality 33.9% vs 43.5% Lactate-guided group HR for mortality, 0.61 More fluid and vasodilators ↓ICU stay ↓ MV duration Jansen et al. Am J Respir Crit Care Med 2010;182:752-61

17. P(v-a)CO2 or CO2 Mallat et al. Worl J Crit Care Med 2016;5:47-56 P(v-a)CO2 (ΔPCO2)  Normal C.O.vs. low C.O.

18. Vasopressors • Hypotension does not necessarily signify impaired organ perfusion and normal BP does not guarantee adequate tissue perfusion. • Because vasopressors induce vasoconstriction (i.e., reducing the radius of vessels), they may reduce organ perfusion despite achieving BP targets. • Clinicians should consider iatrogenic complications.

19. Increasing BP with NE does not improve microcirculatory blood flow. N =20, septic shock Dubin et al Crit Care 2009;13:R92

20. Poiseuille’s Law “Blood flow depends on the radius much rather than the pressure gradient.”

21. Permissive hypotension? • Low tidal volume • Restrictive transfusion • Restricting insulin • Low blood pressure for penetrating trauma • Restrictive fluid for acute lung injury “Adequate perfusion may not depend on “normal BP” and autoregulatory capacity may differ among organs and patient subgroups.” Lamontagne et al. Intensive Care Med 2018;44:87–90

22. ScvO2 Lactate Capillary refill time Urine output Skin mottling Dunser et al Crit Care 2013;17:326

23. Two pilot studies for restricting resuscitation volumes in septic patients CLASSIC study (2016) REFRESH study (2018)

24. 151 septic shock patients who received 30 cc/kg fluid Hjortrup et al. Intensive Care Med 2016;42:1695-705

25. 99 septic shock Vasopressor first Fluid first Fluid (6h) 2387 ml Vasopressors, 21 h Mortality 8% Fluid (6h) 3000 ml Vasopressors, 33 h Mortality 6% Macdonald et al Intensive Care Med 2018;44:2070-78

26. Paradigm shift to “Glycocalyx model” Mathew et al Clin Chest Med 2016;37:241-250

27. Fill the tank ? https://www.memorangapp.com/flashcards/87391/Physiology+L30+Systemic+Circulation+%E2%80%93+II__Venous+return/

28. Conclusions • Resuscitation aimed at normalization of MAP, C.O., and CVP is frequently associated with fluid overload. • Even after improvement of hemodynamics in septic patients, impaired microcirculation still persists. • Tissue perfusion-based approach with lactate and microcirculation, rather than hemodynamic-based one, will become more important. • Increased fluid balance is associated with increased mortality in early and late sepsis; whether conservative fluid management can improve sepsis outcomes requires further study.

29. 감사합니다.

31. Impaired microcirculation is associated with positive fluid balance and increased severity score Microcirculation surrogate: SvcO2max Sturm et al. J Intensive Care Med 2018;33:256-66